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Sci Rep ; 4: 4026, 2014 Feb 07.
Article in English | MEDLINE | ID: mdl-24504028

ABSTRACT

We evaluated homologous recombination deficient (HRD) phenotypes in epithelial ovarian cancer (EOC) considering BRCA1, BRCA2, and RAD51C in a large well-annotated patient set. We evaluated EOC patients for germline deleterious mutations (n = 899), somatic mutations (n = 279) and epigenetic alterations (n = 482) in these genes using NGS and genome-wide methylation arrays. Deleterious germline mutations were identified in 32 (3.6%) patients for BRCA1, in 28 (3.1%) for BRCA2 and in 26 (2.9%) for RAD51C. Ten somatically sequenced patients had deleterious alterations, six (2.1%) in BRCA1 and four (1.4%) in BRCA2. Fifty two patients (10.8%) had methylated BRCA1 or RAD51C. HRD patients with germline or somatic alterations in any gene were more likely to be high grade serous, have an earlier diagnosis age and have ovarian and/or breast cancer family history. The HRD phenotype was most common in high grade serous EOC. Identification of EOC patients with an HRD phenotype may help tailor specific therapies.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , DNA-Binding Proteins/genetics , Neoplasms, Glandular and Epithelial/genetics , Ovarian Neoplasms/genetics , Base Sequence , Carcinoma, Ovarian Epithelial , DNA Methylation/genetics , Female , Homologous Recombination/genetics , Humans , Middle Aged , Mutation , Neoplasms, Glandular and Epithelial/classification , Neoplasms, Glandular and Epithelial/mortality , Ovarian Neoplasms/classification , Ovarian Neoplasms/mortality , Sequence Analysis, DNA
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